Genetic Variant PARD3:p.Ala1337Pro (chr10-34111222-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001184785.2(PARD3):c.4009G>C(p.Ala1337Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,454,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1337V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PARD3
NM_001184785.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.83

Publications

1 publications found

Variant links:

Genes affected

PARD3 (HGNC:16051): (par-3 family cell polarity regulator) This gene encodes a member of the PARD protein family. PARD family members interact with other PARD family members and other proteins; they affect asymmetrical cell division and direct polarized cell growth. Multiple alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Oct 2011]

PARD3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35521233).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARD3	NM_001184785.2 link	c.4009G>C	p.Ala1337Pro	missense_variant	Exon 25 of 25	ENST00000374788.8	NP_001171714.1	Q8TEW0-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARD3	ENST00000374788.8 link	c.4009G>C	p.Ala1337Pro	missense_variant	Exon 25 of 25	1	NM_001184785.2	ENSP00000363920.3		Q8TEW0-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000402

AC:

AN:

248892

AF XY:

0.00000742

show subpopulations

Gnomad AFR exome

AF:

0.0000631

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1454948

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722480

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33296

American (AMR)

AF:

0.00

AC:

AN:

44284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25930

East Asian (EAS)

AF:

0.00

AC:

AN:

39492

South Asian (SAS)

AF:

0.00

AC:

AN:

85930

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53294

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1106982

Other (OTH)

AF:

0.00

AC:

AN:

60004

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 19, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.4018G>C (p.A1340P) alteration is located in exon 25 (coding exon 25) of the PARD3 gene. This alteration results from a G to C substitution at nucleotide position 4018, causing the alanine (A) at amino acid position 1340 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.80

BayesDel_addAF

Benign

-0.078

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

.;.;T;.;.;.;.;.

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

D;D;D;D;D;D;D;D

M_CAP

Benign

0.020

MetaRNN

Benign

0.36

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.97

.;.;L;.;.;.;.;.

PhyloP100

5.8

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.6

N;N;N;N;N;N;N;N

REVEL

Benign

0.21

Sift

Benign

0.13

T;T;T;T;T;T;T;T

Sift4G

Benign

0.14

T;T;T;T;T;T;T;T

Polyphen

0.98

D;.;D;D;D;D;D;.

Vest4

0.76

MutPred

0.17

.;.;Loss of helix (P = 0.0033);.;.;.;.;.;

MVP

0.47

MPC

0.46

ClinPred

0.81

GERP RS

5.3

Varity_R

0.33

gMVP

0.46

Mutation Taster

=61/39

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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10-34111222-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over